Sepsis and Systemic Inflammatory Response Syndrome (SIRS), both refer to a severe biochemical reaction following exposure to an infectious agent (e.g. bacterial toxin such as Anthrax), or from injury or trauma. The systemic response can lead to septic shock, which is characterized by a precipitous drop in blood pressure, cardiovascular collapse, and/or multiple organ failure. Despite the introduction of antibiotics over fifty years ago, the mortality rate among subjects diagnosed with septic shock is 30-50%, higher than that of breast, colon, or prostate cancer. There are approximately 800,000 sepsis cases per year in the U.S. at a cost of $17 billion, with an equal number in the rest of the world. Sepsis and SIRS are increasing rapidly throughout the world due to antibiotic resistance and increased biological threats. The “at risk” population is substantially greater when one considers the potential implications worldwide pandemics (e.g., bird flu) or bioterrorism. In bioterrorism or in battlefield exposure the mortality rates are expected to be much higher. Rapidly and reliably treating sepsis, SIRS, and septic shock has been difficult using conventional medications.
The inter-alpha inhibitor protein (IαIp) family is a group of plasma-associated serine protease inhibitors that modulate the body's response toward the severe systemic inflammation accompanying sepsis, infection, trauma, and injury. Inter-alpha inhibitor protein (IαIp) has been shown to improve the survival or condition of test animals suffering from sepsis;, infected with anthrax, Ebola, or Dengue virus; or suffering from lung injury due to exposure to toxic chemicals or ionizing radiation. IαIp is a large protein that is isolated from blood. Because of the therapeutic use of inter-alpha inhibitor proteins in treating sepsis and SIRS, methods for purifying or preparing IαIp are urgently required.